Alzheimer's disease is characterized by the aggregation of [unreadable]-amyloid (A[unreadable]) protein in the brain, widespread neurodegeneration, and cognitive decline. Our work focuses on amelioration of Alzheimer's pathology by reducing or simplifying the major brain gangliosides aransgenes for amyloid precursor protein (App) and presenilin 1 (Psen1), genes known to cause Alzheimer's disease. In addition, primary neurons from GD3S knockout mice are resistant to A[unreadable]-induced cell death. However, GD3S is absent from birth in these mice, and they lack many of the gangliosides critical for normal brain development. The objective of the proposed studies is to determine whether in vivo degradation of b-series gangliosides and GD1a is as effective as knocking out GD3S in alleviating featuvents memory deficits in mice carrying mutant human transgenes for amyloid precursor protein (App) and presenilin 1 (Psen1), genes known to cause Alzheimer's disease. In addition, primary neurons from GD3S knockout mice are resistant to A[unreadable]-induced cell death. However, GD3S is absent from birth in these mice, and they lack many of the gangliosides critical for normal brain development. The objective of the proa in Alzheimer patients.